Evidence for male-mediated developmental toxicity derives from strong animal data and epidemiological studies, in which exposures of fathers to toxicants are associated with adverse consequences for the fetus and offspring. There is a strong paternal contribution for de novo gene mutations, sex chromosomal aneuploidies and structural aberrations in offspring. The purposes of this study are to examine the effects of benzene, a well-recognized mutagen, on DNA and chromosomal damage in human sperm and to determine the association between chromosomal damage in sperm and blood cells within the same individuals. Although there are a few previous sperm studies on benzene-exposed workers, they are small, have not controlled for potential confounders, and have included highly-exposed workers. In 2004, we conducted the China Benzene and Sperm Study (C-BASS) under the auspices of a prior Superfund grant. We have collected all biologic and environmental samples, including urine, blood, and semen samples and personal air badge monitors, and questionnaire data on 78 workers. Additionally, all sperm and blood genetic assays, including FISH for aneuploidy (X-Y-21), ACM, sperm Comet, Sperm Chromatin Structure Assay (SCSA), and OctoChrome FISH will be completed by June 2006. Delays due to the SARS epidemic in China prevented the earlier initiation and hence, the completion of the data analyses. The specific aims of this project are:1) to determine whether benzene-exposed Chinese workers (n=34) have higher frequencies of sperm with numerical and structural chromosomal defects compared to unexposed Chinese workers (n=34), and to determine if this relationship is dose-related to benzene exposure; 2) to determine whether the same benzene-exposed Chinese workers have more sperm with DNA fragmentation and DNA breaks compared to unexposed workers and to determine if this relationship is dose- related to benzene exposure; and 3) to determine whether benzene-exposed workers compared to unexposed workers have higher frequencies of aneuploidy and aberrations in lymphocytes and whether these chromosomal abnormalities are associated with similar defects in sperm. This project will contribute towards understanding the reproductive health of men exposed to benzene, by understanding whether benzene exposure is associated with production of a higher frequency of genetically- defective sperm and, indirectly, with the potential for an increased risk for paternally-mediated developmental effects in offspring. We will also add to the body of information necessary for risk assessment by determining whether benzene exposures represent a risk at doses nearer to those that are permissible in US workers than examined in previous studies. Lastly, this study is one of the first to investigate the relative sensitivities of sperm and blood cells to chromosomal defects induced by benzene. [unreadable] [unreadable] [unreadable]